caseofmulpleirae% · 2019. 7. 23. · pred 40 start beta blockade for symptomatic tachycardia?...
TRANSCRIPT
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Case of Mul+ple IrAE
Michael Postow, MD Memorial Sloan Ke=ering Cancer Center
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Disclosures
Advisory Board: Array BioPharma, Aduro, BMS, Incyte, Merck, NewLink Genetics, Novartis
Honoraria: BMS and Merck
Institutional Support: RGenix, Infinity, BMS, Merck, Array BioPharma, Novartis
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67 year old man with metasta+c mucosal melanoma and brain metastases
6/14/18: Started nivolumab (1mg/kg) + ipilimumab (3mg/kg)
Had a rash after dose 1-- triamcinolone cream.
7/5/2018: Dose 2 of nivolumab + ipilimumab
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Fever, tachycardia, and fa+gue
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Fever, tachycardia, and fa+gue
7/10/2018: Presented to a local Emergency Department with a fever of 101 degrees Fahrenheit and HR 140.
Labs notable for AST 240 (37 is nl); ALT 185 (55 is nl); bilirubin and alkaline phosphatase normal. CBC normal.
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Admit for monitoring?
Hydrate, NSAIDs for fever, discharge with close LFT follow-‐up?
Evaluate for other irAE?
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Fever, tachycardia, and fa+gue
EKG showed atrial fibrillation at 140
Patient was admitted
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TSH 0.02 (0.60 is lower limit of nl) Free T4 4.45 (up to 1.9 is nl)
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TSH 0.02 (0.60 is lower limit of nl) Free T4 4.45 (up to 1.9 is nl)
Start anti-thyroid medication for hyperthyroidism (methimazole or propylthiouracil)?
Start steroids for hyperthyroidism and LFTs?
Start beta blockade for symptomatic tachycardia?
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TSH 0.02 (0.60 is lower limit of nl) Free T4 4.45 (up to 1.9 is nl)
Start anti-thyroid medication for hyperthyroidism (methimazole or propylthiouracil)?
Start steroids for hyperthyroidism and LFTs? Pred 40
Start beta blockade for symptomatic tachycardia? Propranolol
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OVen hyperthyroid (thyroidi+s) then hypothyroid
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Atrial fib and LFTs resolved, tapered from steroids over 3 weeks
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Atrial fib and LFTs resolved, tapered from steroids over 3 weeks
Mid-August 2018: Epigastric abdominal pain and nausea without diarrhea
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Atrial fib and LFTs resolved, tapered from steroids over 3 weeks
Epigastric abdominal pain and nausea without diarrhea
Steroid induced gastritis?
Recurrence of hepatitis?
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Atrial fib and LFTs resolved, tapered from steroids over 3 weeks
Amylase and lipase elevated 8x upper limit of normal
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Immunotherapy related pancrea++s
Steroids increased to 70mg daily
Hyperglycemia to 200s requiring metformin
8/29/18 Infliximab #1 (5mg/kg) and steroids weaned
9/12/18 Infliximab #2 (5mg/kg)
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Infliximab does not seem to affect efficacy of ipilimumab
Arriola et al. Clin Cancer Res 2015
Retrospec+ve study of 113 pa+ents 32 pa+ents with diarrhea (19 pa+ents Grade ≥ 2 diarrhea) 29 pa+ents received steroids 7 pa+ents had infliximab
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Schadendorf, …. and Postow JCO 2017
Outcomes look similar in pa+ents who discon+nue due to toxicity vs. those who
con+nue treatment longer
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Schadendorf, …. and Postow JCO 2017
Outcomes look similar in pa+ents who discon+nue due to toxicity vs. those who
con+nue treatment longer
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Summary of Case
• Many organs can be involved and watch for new irAE on steroid taper
• Transient immunosuppression does not hurt immunotherapy benefit (except maybe prednisone >7.5mg daily in hypophysi+s)
• Unclear how much immunotherapy is needed for benefit
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Thank you!
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Back-‐up Slides
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Sznol et al. Journal of Clin Oncol 2017
Most side effects resolve